The incidence of migraine is said to be in the region of 12% of the population. Its precise causes have not been determined but certain elements in its causation are well documented.
Neurohumoral and local hormone (autacoid) factors such as noradrenaline, 5-hydroxytryptamine (serotonin), histamine and prostaglandins are implicated in migraine probably acting at the cerebro-vascular level.
There is much evidence to suggest that a disturbance of blood vessel diameter is involved in the migraine process. Thus reports have demonstrated a constriction of cerebral cortical vessels followed by a dilatation during a migraine attack. The vasoconstriction is believed to be due to the release of amines such as noradrenaline from neurones and 5-hydroxytryptamine from platelets. Histamine is also released from mast cells and plays an important role in the migraine variant known as cluster headache (migrainous neuralgia). Drugs with antinoradrenaline, anti 5-hydroxytryptamine and antihistamine activities are all used to alleviate the symptoms of migraine. Evidence that prostaglandins (PG), such as PGE.sub.2, PGF.sub.2.alpha., PGI.sub.2 (prostacyclin) or thromboxane A.sub.2 are involved comes from the fact that non-steroidal anti-inflammatory drugs such as aspirin, which act by inhibiting the synthesis of prostaglandins, are highly effective for both the prophylactic and acute treatment of migraine.
As to the causes of arthritic conditions, the suppression of prostaglandin synthesis by non-steroidal anti-inflammatory drugs such as aspirin or indomethacin strongly implicates prostaglandins as inflammatory mediators at least in rheumatoid arthritis. Prostaglandin-like material is present in inflammatory perfusates of experimental animals. The E-prostaglandins in low concentrations are striking potentiators of the pain-producing properties of other agonists such as histamine, 5-hydroxytryptamine and plasmakinins (e.g. bradykinin) as well as other features of the inflammatory response such as increased vascular permeability, erythema, white cell accumulation and platelet aggregation.
Patients with bronchial asthma and chronic bronchitis suffer attacks of wheezing and difficulty in breathing. These are due to bronchial narrowing from spasm of the bronchial smooth muscle or from sticky secretions, or more commonly from a combination of the two. The precise causes of the bronchoconstriction in asthma have not been fully elucidated, but it is believed endogenous neurohumoral and autocoid spasmogens such as acetylcholine, 5-hydroxytryptamine (serotonin), histamine, some prostaglandins and leukotrienes may be involved. Allergic reactions to substances in inhaled dust or those absorbed from food may be manifested by bronchoconstriction or urticaria ("nettle-rash") or circulatory collapse caused by the release of histamine or other endogenous substances.
Drugs with spasmolytic actions such as aminophylline are used to treat bronchospasm. Drugs with antihistamine activity are also used in asthma and for wheezing and other symptoms associated with allergic phenomena such as hay fever.
It has been known for many years that sesquiterpene lactones are present in plants, for example, in the family Compositae (see Yoshio, Mabry and Timmermann, "Sesquiterpene Lactones, Chemistry, NMR and Plant Distribution", University of Tokyo Press 1973).
Of these plant Tanacetum parthenium (formerly called Chrysanthenum parthenium and commonly known as feverfew, featherfoil, flirtwort and Bachelor's Buttons) has been put forward in herbal medicine as a possibly effective treatment for migraine when consumed. No serious medical study of this treatment for migraine has apparently been published, nor has there been any consideration of what ingredient or ingredients of the plant might be involved in this alleged efficacy.
Many years ago, it was reported that the sesquiterpene lactones parthenolide and santamarine may be extracted from feverfew using light petroleum and chloroform respectively (see Sorm et al, Coll. Czech. Chem. Comm., (1961), 26, 803 and Romo et al, Tetrahedron, (1965), 21, 1741 respectively). In those publications, there was no indication of any possible medical use for the sesquiterpene lactones.
Some cytotoxic activity of parthenolide and several other sesquiterpene lactones has also been reported some time ago (Lee et al, Cancer Research, (1971), 31, 1649). There is, however, no suggestion in this article that any sesquiterpene lactone or extract containing it may be useful in the treatment of migraine, arthritis or bronchial complaints.
More recently it has been shown that certain sesquiterpene lactones are potent inhibitors of carrageenan-induced edema and chronic adjuvant-induced arthritis in rodents (see Hall, Starnes, Lee and Waddell, J. Pharm. Sci., (1979), 68,537). This article does not, however, suggest that any sesquiterpene lactone has pharmaceutical activity against any complaint, let along against migraine.